This application seeks to renew project R01 HD047315, which supported the conduct of a randomized clinical trial of a high level of supplementation of docosahexaenoic acid (DHA) during the prenatal period (ClinicalTrials.gov ID: NCT00266825). We achieved the enrollment and follow-up goals of the original RCT and, most importantly for the current proposal, we have retained the planned large cohort of children born to women enrolled in the parent trial. Infants enrolled and followed to 18 months of age in this trial are now entering a particularly important period of cognitive and intellectual development, and the successful retention of the current sample allows for an unprecedented opportunity to determine if prenatal supplementation of DHA affects preschool and school-age outcomes that predict successful school performance and adaptive behaviors. The different skills that emerge at these ages build on early components of cognition, which have been positively associated with higher DHA status in both observational studies and clinical trials. We propose to test these infants on a semi-annual basis from 24 through 72 months of age employing outcomes that assess four domains of development that are critical to health, adjustment, and well-being through adulthood: (a) higher-order cognition (memory, attention, and executive function), (b) language processing and preliteracy skills, (c) adaptive regulation (self-regulation skills related to behavioral problems, school performance, and child psychopathology), and (d) intelligence. The proposed assessments will allow us to determine whether prenatal nutritional supplementation with DHA affects child health and development. The findings could contribute to evidence-based policy on prenatal nutrition. In addition, the evidence from this renewal would address hypotheses concerning fetal programming and human behavior that are currently at the forefront within the field of health, development and nutrition. PUBLIC HEALTH RELEVANCE: The current project seeks to determine whether prenatal nutritional supplementation to docosahexaenoic acid (DHA) affects developmental outcomes related to intelligence and school readiness. The possibility that nutritional compounds provided in utter may have long-term implications for meaningful measures that bear on cognitive-intellectual development and on measures that are directly related to or predictive of school achievement would have enormous implications for the formulation of public policy on prenatal nutrition. Furthermore, the data collected here would bear on hypotheses concerning the possibility that environmental events or conditions occurring early in life contribute to long-term status of biological or physiological mechanisms. As such, the data would also have major implications for consideration how conditions of the prenatal environment determine long-term outcomes in health and welfare.